The pituitary glycoprotein hormones, follitropin (FSH) and lutropin (LH), are known to be secreted in response to the hypothalamic releasing hormone GnRH. They act on the gonads which in turn product hormones that act as feedback inhibitors. The feedback inhibition of LH is almost entirely due to the action of gonadal steroids, whereas that of FSH is though to be due in part to the action of the gonadal glycoprotein hormone, inhibin, and in part to gonadal steroids.
Inhibin has recently been purified to homogeneity and its primary structure determined from gene sequencing. It is a member of a gene family which includes Mullerian inhibiting substance (MIS) and transforming growth factor-.beta. (TGF-.beta.). Inhibin is a heterodimer composed of an A or .alpha. subunit and a B or .beta. subunit and in certain species, there are two types of .beta. subunit designated .beta..sub.A and .beta..sub.B giving rise to .alpha..beta..sub.A and .alpha..beta..sub.B forms of inhibin.
Surprisingly, .beta..sub.A homodimers and .beta..sub.A .beta..sub.B heterodimers were found to exist in follicular fluid and to have an effect opposite to that of inhibin. That is, they act to stimulate FSH synthesis and release and have been termed "activin" [Ling et al (1986) Nature 321 779-782] or "FRP" (FSH-releasing peptide) [Vale et al (1986) Nature 321 776-779]. An overview of the field is given by Tsonis and Sharpe (1986) Nature 321, 724-725.
The current invention provides the isolation of a second proteinaceous molecule with FSH-suppressing activity termed FSH-suppressing protein (FSP).
Since FSP can suppress FSH levels, FSP will be useful as a contraceptive agent in both sexes; in promoting fertility either by immunisation or by using the rebound effect in FSH levels following FSP administration; or as a diagnostic aid in monitoring gonadal function. However, it is to be noted that whilst this protein has been purified on the basis of its suppression of pituitary FSH production and named FSP, it does not exclude the fact that it may also have major activities (including those of growth factor/differentiation factor) other than that implied by its name. For example, MIS also acts as an oocyte meiosis inhibitor and TGF-.beta. has an FRP/activin-like activity.